Pharmacological characterization of cannabidiol as a negative allosteric modulator of the 5-HT receptor.

Promising clinical evidence suggests that psychedelic compounds, like lysergic acid diethylamide (LSD), have therapeutic value for treatment of psychiatric disorders. However, they often produce hallucinations and dissociative states, likely mediated by the serotonin (5-HT) receptor 5-HT, raising challenges regarding therapeutic scalability. Given the reported antipsychotic effects of cannabidiol (CBD) and its promiscuous binding at many receptors, we assessed whether CBD could modulate 5-HT signalling.

Amblyopic binocular imbalance quantified by the dichoptic contrast ordering test and dichoptic letters test.

In amblyopia, abnormal binocular interactions lead to an overwhelming dominance of one eye. One mechanism implied in this imbalance is the suppression between the inputs from the two eyes. This interocular suppression involves two components: an overlay suppression and a surround suppression.

Identification of a Founder GLDN Variant Associated With "Lethal" Arthrogryposis in Nunavik Inuit: Implications for Obstetrical and Long-Term Survivors' Management.

Biallelic variants in GLDN have recently been associated with lethal congenital contracture syndrome 11 (LCCS11), a form of fetal akinesia deformation sequence (FADS) with high neonatal mortality. In this report, we describe five individuals from two Canadian Inuit families originating from different communities in Nunavik all affected with FADS and harboring a rare homozygous missense variant, [NM_181789.4:c.

Comparing machine learning techniques for neonatal mortality prediction: insights from a modeling competition.

Background: Predicting mortality risk in neonatal intensive care units (NICUs) is challenging due to complex, variable clinical and physiological data. Machine learning (ML) offers potential for more accurate risk stratification.

Objective: To compare the performance of various ML models in predicting NICU mortality using a team-based modeling competition.

Flavokavains A- and B-Free Kava Enhances Resilience against the Adverse Health Effects of Tobacco Smoke in Mice.

Tobacco smoke remains a serious global issue, resulting in serious health complications, contributing to the onset of numerous preventive diseases and imposing significant health burdens. Despite regulatory policies and cessation measures aimed at curbing its usage, novel interventions are urgently needed for effective damage reduction. Our preclinical and pilot clinical studies showed that AB-free kava has the potential to reduce tobacco-smoking-induced lung cancer risk, mitigate tobacco dependence, and reduce tobacco use.

Central auditory processing and cognitive abilities after mild traumatic brain injury in school-aged children.

Objective: The current study aimed to explore (1) school-aged children's auditory and cognitive abilities and (2) their perceptions (self-reported and parents) of listening behaviours and symptoms following mild traumatic brain injury (mTBI).

Design: Prospective cohort study.

Study Sample: Twenty-one children aged 8 to 12 participated in this study.

Characterization of Incident Interstitial Lung Disease in Late Systemic Sclerosis.

Objective: Interstitial lung disease (ILD) is a common and potentially lethal complication of systemic sclerosis (SSc). Screening by high-resolution computed tomography (HRCT) is recommended in all patients with risk factors, including early disease. Little is known on late presentations of ILD.

Optimizing use of an electronic medical record system for quality improvement initiatives in hemodialysis: Review of a single center experience.

Introduction: The complexity of managing patients with end-stage kidney disease on hemodialysis underscores the importance of implementing quality improvement (QI) initiatives to enhance patient safety and prioritize patient-centered care. To address this, we established a QI committee at our tertiary academic center focusing on evidence-based practices, patient-centered approaches, and cost efficiency. To facilitate the seamless implementation of QI initiatives, we leveraged the capabilities of our electronic medical record (EMR) system.

Quality of Life in People With HIV at the End of Life: Preliminary Results From the Last Gift Observational Cohort Study.

Background: As people living with HIV (PWH) age, they face new challenges that can have a negative impact on their quality of life (QOL) and mental health.

Setting: This study enrolled PWH at the end of life (EOL) who were actively engaged in cure-related research in Southern California, United States. EOL was defined as having a prognosis of 6 months or less to live.

The psychometric properties of the Quality of Life in Neurological Disorders (Neuro-QoL) measurement system in neurorehabilitation populations: a systematic review.

Objective: To systematically review the literature of existing evidence on the measurement properties of the Quality of Life in Neurological Disorders (Neuro-QoL) measurement system among neurorehabilitation populations.

Data Sources: The Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) guided this systematic review in which we searched nine electronic databases and registries, and hand-searched reference lists of included articles.

Study Selection: Two independent reviewers screened selected articles and extracted data from 28 included studies.

Disentangling the Effects of Comorbidity and Polypharmacy on Cognitive Function and Physical Frailty in Individuals With HIV.

Objective: To estimate the extent to which comorbidity, polypharmacy, and anticholinergic/sedative burden interrelate to influence cognitive ability, perceived cognitive deficits (PCD), and physical frailty in people living with HIV.

Design: Cross-sectional Structural Equation Modeling of data from 824 older people living with HIV in Canada, participating in the Positive Brain Health Now study.

Method: Structural Equation Modeling was used to link observed variables, including comorbidity, polypharmacy, anticholinergic, and sedative burden, to cognitive ability and 2 latent constructs-physical frailty and PCD.

Acute and Reversible Hypothalamic Symptoms in a Lateral Head Impact Mouse Model of Mild Traumatic Brain Injury.

Central autonomic and endocrine dysfunctions following traumatic brain injury (TBI) are believed to involve the hypothalamus; however, underlying mechanisms are unknown. Although chronic deficits might be caused by irreversible tissue damage, various neuroendocrine and autonomic symptoms are only observed transiently, suggesting they might result from a temporary alteration in the activity of hypothalamic neurons. We therefore examined if a mouse model of mild TBI could induce reversible autonomic phenotypes and cause acute changes in c-Fos expression within corresponding regions of the hypothalamus.

Autism-associated CHD8 controls reactive gliosis and neuroinflammation via remodeling chromatin in astrocytes.

Reactive changes of glial cells during neuroinflammation impact brain disorders and disease progression. Elucidating the mechanisms that control reactive gliosis may help us to understand brain pathophysiology and improve outcomes. Here, we report that adult ablation of autism spectrum disorder (ASD)-associated CHD8 in astrocytes attenuates reactive gliosis via remodeling chromatin accessibility, changing gene expression.

Defining the functional properties of cyclopropane fatty acid synthase from Pseudomonas aeruginosa PAO1.

Cyclopropane fatty acid synthases (CFAS) catalyze the conversion of unsaturated fatty acids to cyclopropane fatty acids (CFAs) within bacterial membranes. This modification alters the biophysical properties of membranes and has been correlated with virulence in several human pathogens. Despite the central role played by CFAS enzymes in regulating bacterial stress responses, the mechanistic properties of the CFAS enzyme family and the consequences of CFA biosynthesis remain largely uncharacterized in most bacteria.

Exploring Potential Gender-Based Disparities in Referral for Transplant, Activation on the Waitlist and Kidney Transplantation in a Canadian Cohort.

Introduction: In the United States, women are less likely to be referred, activated on the waitlist, or undergo kidney transplant (KT) than men; contemporary Canadian data regarding access to transplant for women are lacking.

Methods: Among patients initiating dialysis in Nova Scotia (NS), Canada from 2010 to 2020, we examined the association of candidate gender with overall access to KT, including the following: (i) odds of transplant referral within 1 year of dialysis initiation, (ii) odds of activation on the transplant waitlist (if referred), and (iii) time-to-transplantation (if activated) using logistic regression or Cox proportional hazards models as appropriate.

Results: Among 749 patients deemed potentially eligible for transplant, women had lower transplant rates than men (adjusted hazard ratio [aHR]: 0.

Estrogen Receptor Blockade Potentiates Immunotherapy for Liver Metastases by Altering the Liver Immunosuppressive Microenvironment.

Unlabelled: Liver metastases (LM) remain a major cause of cancer-related death and are a major clinical challenge. LM and the female sex are predictors of a poorer response to immunotherapy but the underlying mechanisms remain unclear. We previously reported on a sexual dimorphism in the control of the tumor microenvironment (TME) of colorectal carcinoma liver metastases (CRCLM) and identified estrogen as a regulator of an immunosuppressive TME in the liver.

The use of cap-mounted clips as a primary hemostatic modality in nonvariceal upper gastrointestinal bleeding: A systematic review and meta-analysis of randomized trials.

Background: Cap-mounted-clips, especially Over-The-Scope-Clip (OTSC™), are recommended for recurrent nonvariceal upper gastrointestinal bleeding (NVUGIB). There has been recent interest in their use as an initial hemostatic modality. We performed a systematic review of randomized controlled trials (RCTs) assessing cap-mounted clips' efficacy as a primary hemostatic modality in NVUGIB.

Early rhombic lip Protogenin stem cells in a human-specific neurovascular niche initiate and maintain group 3 medulloblastoma.

We identify a population of Protogenin-positive (PRTG) MYC NESTIN stem cells in the four-week-old human embryonic hindbrain that subsequently localizes to the ventricular zone of the rhombic lip (RL). Oncogenic transformation of early Prtg rhombic lip stem cells initiates group 3 medulloblastoma (Gr3-MB)-like tumors. PRTG stem cells grow adjacent to a human-specific interposed vascular plexus in the RL, a phenotype that is recapitulated in Gr3-MB but not in other types of medulloblastoma.